APP and familial Alzheimer disease: Rare familial cases of AD (FAD) are caused by mutations of the amyloid precursor protein gene (APP) or of some of the proteins forming the γ-secretase enzyme complex (PSEN1, coding for presenilin 1, PSEN2, coding for presenilin 2) while the vast majority of AD cases are sporadic, late-onset forms of the disease, suggesting that environmental factors may play a role in etiology.